This project consists of studies of the life cycle of the human retroviruses at the molecular level and their application to the development of approaches to antiviral therapy. Studies are currently underway in the following areas: I) studies of antisense oligonucleotides against the viral regulatory genes and gag gene; 2) development of possible gene therapy treatments directed against tat using a retroviral delivery system; 3) development of possible delivery systems for antiviral genes, including adeno-associated virus, naked DNA, and adenoviruspolylysine conjugates; 4) inhibition of human immunodeficiency virus type 1 (HIV-1) by intracellular antibodies; and 5) characterization of the role of HIV-1 integrase and integration, in viral replication and expression.